Chapter 15 Radical Reactions. Radicals are reactive species with a single unpaired electron, formed by



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Chapter 15 Radical Reactions Radicals are reactive species with a single unpaired electron, formed by homolysis of a covalent bond; a radical contains an atom that does not have an octet of electrons, making it reactive and unstable. 3 C + Radical processes involve single electrons; hence one half-headed arrows are used to show the movement of each electron. Bond dissociation energies for the cleavage of C- bonds are used as a measure of radical stability. eavage of the weaker bond forms the more stable radical: C 2 C 2 C 2 C 2 +! = +98 kcal/mol 1 radical C C +! = +95 kcal/mol 2 radical ence a 2 radical is more stable than a 1 radical. Carbon radicals are trigonal planar and sp 2 -hyridized; their stabilities increase with increasing alkyl substitution but resonance stabilization is even more important: < RC 2 < R 2 C < R 3 C < 2 C C C 2 methyl 1 2 3 sp 2 -hybridized increasing radical stability Radicals are formed from covalent bonds by adding energy in form of heat or light, or by use of a radical initiator, a compound that contains a fairly 1

weak bond that serves as a source of radicals; Peroxides, R R, are commonly used as radical initiators. Radicals react by two main pathways; they react with σ bonds or they add to π bonds, in both instances achieving an octet of electrons. Two radicals can also react with one another, each donating one electron. alogenation of Alkanes C + X 2 C X + X X = or - useful reaction only for 2 and 2 ; the reaction with F 2 is too violent and reaction with I 2 is too slow to be useful - alkyl halides are formed. For example, + 2 C 2 all halogenation reactions proceed by a radical chain mechanism, which has three distinct parts. Using chlorination of ethane as an example: initiation: 2 propagation: forms the reaction products C 2 + C 2 + (2) C 2 + C 2 + (3) repeat steps 2 and 3 over and over; no additional initiation required termination: 2 radicals react to form a σ bond, removing reactive radicals and hence preventing further propagation 2

+ 2 C 2 + C 2 C 2 + C 2 C 2 C 2 - formation of C 2 C 2 is evidence of a radical chain mechanism early, the propagation steps are most important in a radical chain mechanism since they lead to product formation. A look at enthalpy changes for the propagation steps of ethane chlorination shows that the first propagation step is rate-determining see Figs 15.3 and 15.4 the transition state for the first propagation step is higher in energy than the transition state for the second propagation step since we have to break a stronger bond (C-) in the first step than in the second step (- ). Chlorination of higher alkanes: chlorination of propane gave a 1:1 mixture of two products, 1-chloropropane (formed by abstraction of a primary hydrogen) and 2-chloropropane (formed by abstraction of a secondary hydrogen). 2 C 2 + 2 2 C 2 C 2 + CC 2 1 : 1 + 2 If all the C bonds in C 2 were equally reactive then a 3:1 mixture of 1-chloropropane and 2-chloropropane would be expected on statistical grounds. The observed 1:1 ratio of products clearly indicates that it is easier to homolytically cleave a 2 C bond than a 1 C bond. In fact, we know that the weaker the C- bond, the more readily the hydrogen is 3

removed in radical halogenation. That is, ease of abstraction follows the order: < RC 2 < R 2 C < R 3 C. Chlorination versus omination - chorination is faster than bromination but chlorination is unselective (yields a mixture of products) while bromination is often selective, giving one major product. In bromination, the major (and sometimes exclusive) product results from cleavage of the weakest C- bond. For example, 2 C 2 + 2 2 C 2 C 2 + CC 2 1 : 1 + 2 versus 2 C 2 + 2 2 C 2 C 2 + CC 2 1% : 99% + 2 To understand the difference in selectivities of chlorination and bromination reactions, we must compare the rate-determining step of alkane halogenation reactions, which is abstraction of a hydrogen atom by the halogen radical. The rate-determining step in bromination is endothermic hence the more stable radical is formed faster (since it takes less energy to form it), and often a single radical halogenation product predominates (transition state of an endothermic reaction resembles the products ammond postulate). C 2 C 2 + C 2 C 2 +! = +10 kcal/mol +98 kcal/mol 1 radical -88 kcal/mol 4

C + +95 kcal/mol C 2 radical + -88 kcal/mol! = +7 kcal/mol See also Figure 15.5. The rate-determining step in chlorination is exothermic hence the transition state resembles reactants, both radicals are formed and a mixture of products are formed. C 2 C 2 + C 2 C 2 +! = -5 kcal/mol +98 kcal/mol 1 radical -103 kcal/mol C + +95 kcal/mol C 2 radical + -103 kcal/mol! = -8 kcal/mol See also Figure 15.6. Alkane halogenation is a useful tool in organic synthesis since it allows conversion of an unreactive alkane molecule into an alkyl halide, which can then be elaborated into more complex molecules; e.g. 3 C C + 2! or h! 3 C C KBu t 3 C 3 C C C 2 Stereochemistry of alogenation reactions - halogenation of an achiral starting material always forms an achiral or a racemic product see page 548 - if radical halogenation of a chiral starting material occurs at a stereogenic center, racemization at the stereogenic center occurs see page 549 5

- if halogenation of a chiral starting material does not occur at a stereogenic center, the configuration of the stereogenic center is retained in the product see page 549 Selective omination at allylic C- bonds As mentioned earlier, an allylic radical is even more stable than a 3 radical because an allylic C- bond is weaker than other sp 3 -hydridized C- bonds. NBS h! or RR NBS = N-omosuccinimide = N -the allylic carbon can be selectively brominated using NBS in the presence of light or peroxides; e.g. the allyic C- bond in cyclopentene reacts to form an allylic bromide, via a radical chain mechanism: Initiation propagation N h! or RR N + + + + + ˇ In addition to acting as a source of radical, NBS also generates a low concentration of 2 needed in the second chain propagation step 6

N + N + 2 low concentration of 2 favors allylic substitution over 2 addition to the C=C bond by ensuring low concentrations of the bromonium- and - ion intermediates that are characteristic of the addition reaction (see section 10.13). Thus, 2 NBS h! or RR - whenever two different resonance structures can be drawn for an allylic radical, two different allylic halides are formed by radical substitution; hence halogenation at an allylic carbon often results in a mixture of products. E.g. NBS h! + 2 2 - problem for class: which of these two compounds can be prepared in good yield by allylic halogenation of an alkene? 2 1 2 7

Addition to Alkenes adds to alkenes to form alkyl bromides in the presence of light, heat, or peroxides; e.g. ( 3 C) 2 C C h! ( 3 C) 2 C C Notice that bonds to the less substituted carbon. In contrast, addition to an alkene without added light, heat, or peroxide occurs by hydrogen addition to the less substituted carbon; e.g. ( 3 C) 2 C C ( 3 C) 2 C C 2 - this is because this reaction proceeds via carbocation intermediates (see section 10.10). A chain mechanism accounts for the regioselectivity of radical addition of to an alkene: the more stable radical forms faster initiation h! + propagation ( 3 C) 2 C C ( 3 C) 2 C C 3 radical ( 3 C) 2 C C ( 3 C) 2 C C + termination + 2 In radical addition of to an alkene, adds first to generate the more stable radical while in ionic addition of to an alkene, + adds first to generate the more stable carbocation. 8

Unlike addition, and I do not add to an alkene under radical conditions. Studies of energy changes in the reactions show that both propagation steps are exothermic for addition hence propagation is energetically favorable. In contrast, the first propagation step is exothermic but the second step is endothermic for addition, while the first propagation step is endothermic but the second step is exothermic for I addition. Since one of the two propagation steps is endothermic for and I addition, the radical reaction cannot successfully compete with the termination steps. Radical Polymerization Polymers are macromolecues made up of repating units of smaller molecules called monomers. Radical polymerization of alkene monomers occurs by a chain mechanism e.g. n R-R n polystyrene radical stability enforces head to tail polymerization that is, the more substituted radical always adds to the less substituted end of the monomer 9

initiation R R 2 R R R carbon radical propagation R R termination + The zone Layer and CFC s 2 + 3 + heat 3 2 + The formation of ozone from 2 and atoms in the upper atmosphere and its decomposition back to 2 and atoms essentially has the effect of converting uv radiation into heat. Thus, protecting the earth s surface from harmful uv radiation. CFC s decompose in the upper atmospheres to form radicals that destroy ozone by a radical chain mechanism, e.g.: Initiation - CF 3 --hν- CF 2 + Propagation - 3 + - + 2 - + + 2 10

The overall result is that 3 is consumed and 2 is formed. CFC s and FC have replaced CFC s because they are decomposed by before they reach the stratosphere and cause ozone depletion. 11